Value Proposition
· Comprehensive toolkit for mechanoreceptor research: Five complementary mouse strains that enable precise visualization, manipulation, and functional analysis of different mechanoreceptor populations and neural development pathways
· Genetic precision: Each strain targets specific cell populations (Aδ-LTMRs, trigeminal neurons, thalamocortical projections) with high specificity, enabling researchers to study individual components of complex neural circuits
· Conditional control: Multiple strains offer Cre-lox and tamoxifen-inducible systems, allowing temporal and spatial control over gene expression and cell labeling
· Addresses multiple research areas: Enables studies in somatosensation, neural development, axon guidance, mechanotransduction, and peripheral nervous system patterning
Unmet Need
Understanding the development and function of the peripheral nervous system, particularly mechanoreceptors and sensory neurons, requires precise tools to visualize and manipulate specific cell populations during development and in adult animals. Current approaches often lack the specificity needed to study individual mechanoreceptor subtypes or rely on broad markers that cannot distinguish between functionally distinct populations. Existing methods also frequently cannot provide temporal control over when genetic modifications occur, limiting researchers' ability to study developmental processes or adult function independently. Therefore, there is a strong need for validated, specific genetic tools to be developed to address the precise study of mechanoreceptor development, function, and neural circuit formation.
Technology Description
Researchers at Johns Hopkins have developed five genetically engineered mouse strains to study mechanoreceptors and peripheral nervous system development. The technology includes strains for visualizing Aδ-low-threshold mechanoreceptors (TrkBtauEGFP), conditional manipulation of BMP4 signaling modulator MEGF8, studying thalamocortical projections through ISLR2/Linx, and tamoxifen-inducible Cre expression in TrkB-positive neurons (TrkBCreER). These tools work by inserting fluorescent reporters, conditional alleles, or Cre recombinase systems into genes critical for mechanoreceptor function and neural development, enabling researchers to track, manipulate, and analyze specific cell populations with high precision.
Stage of Development
· These mutant mouse strains are available on Jax Lab’s repository:
o 023046 B6.129S6(Cg)-Ntrk2tm2.1Ddg
o 025417 STOCK Megf8tm1.2Ddg
o 025418 C3;B6-Megf8m687Ddg
o 025615 STOCK Islr2tm2.1Ddg
o 027214 B6.129S6(Cg)-Ntrk2tm3.1(cre/ERT2)Ddg
Data Availability
· n/a
Publication
· 023046 B6.129S6(Cg)-Ntrk2tm2.1Ddg/J Li L; Rutlin M; Abraira VE; Cassidy C; Kus L; Gong S; Jankowski MP; Luo W; Heintz N; Koerber HR; Woodbury CJ; Ginty DD. 2011. The functional organization of cutaneous low-threshold mechanosensory neurons. Cell 147(7):1615-27. [PubMed: 22196735] [MGI Ref ID J:196548]
· 025417 STOCK Megf8tm1.2Ddg/J Engelhard C; Sarsfield S; Merte J; Wang Q; Li P; Beppu H; Kolodkin AL; Sucov HM; Ginty DD. 2013. MEGF8 is a modifier of BMP signaling in trigeminal sensory neurons. Elife 2:e01160. [PubMed: 24052814] [MGI Ref ID J:206541]
· 025418 C3;B6-Megf8m687Ddg/J Engelhard C; Sarsfield S; Merte J; Wang Q; Li P; Beppu H; Kolodkin AL; Sucov HM; Ginty DD. 2013. MEGF8 is a modifier of BMP signaling in trigeminal sensory neurons. Elife 2:e01160. [PubMed: 24052814] [MGI Ref ID J:206541]
· 025615 STOCK Islr2tm2.1Ddg/J Mandai K; Reimert DV; Ginty DD. 2014. Linx Mediates Interaxonal Interactions and Formation of the Internal Capsule. Neuron :. [PubMed: 24930700] [MGI Ref ID J:210221]
· 027214 B6.129S6(Cg)-Ntrk2tm3.1(cre/ERT2)Ddg/J Liu Y; Rutlin M; Huang S; Barrick CA; Wang F; Jones KR; Tessarollo L; Ginty DD. 2012. Sexually dimorphic BDNF signaling directs sensory innervation of the mammary gland. Science 338(6112):1357-60. [PubMed: 23224557] [MGI Ref ID J:192549]
